Improving outcomes for HIV-infected children in South Africa and Cote d'Ivoire

描述(由申请人提供)：及时诊断和治疗儿童艾滋病毒感染的方案在降低撒哈拉以南非洲儿童死亡率方面发挥着关键作用。临床领导人和政策制定者需要了解这些计划的长期好处和成本，不同类型的艾滋病毒流行环境可能会有所不同。南非是一个中等收入国家，艾滋病毒感染率非常高(30%：“普遍的”艾滋病毒流行)，感染艾滋病毒的妇女及其婴儿可以很好地获得卫生服务。科特迪瓦是一个低收入国家，艾滋病毒感染率较低(3%：艾滋病毒“混合”流行)，获得与艾滋病毒有关的卫生服务的机会较为有限。这两个国家代表了撒哈拉以南非洲艾滋病毒流行的两种主要类型。儿科艾滋病毒治疗的长期结果反映了数十年来的连续事件，因此不能使用临床试验或队列研究等传统方法进行全面调查。计算机模型可以通过预测短期和长期范围内的生存和医疗资源利用情况，为短期临床研究增加巨大价值；这可以帮助临床医生和政策制定者在许多相互竞争的有限资源需求中确定优先顺序。此外，计算机模型可以确定对生存和成本影响最大的因素，从而为未来的研究勾勒出关键的优先事项。通过K01 AI078754和IMPAACT网络，NICHD、NIAID和NIMH已经支持了儿童HIV疾病的初步模型-预防艾滋病并发症的成本效益(CEPAC)-儿科模型。我们组建了一支在儿科艾滋病毒、模拟建模和流行病学方面具有专长的国际研究小组，我们使用CEPAC-儿科模式对预防儿童艾滋病毒感染的战略进行了分析，这些战略为世卫组织的指导方针提供了参考。我们现在建议对CEPAC-儿科模型进行重大扩展，并使用我们的模型来评估在南非和科特迪瓦诊断和治疗儿科艾滋病毒的新策略。我们的三个具体目标是：1)确定对早期婴儿艾滋病毒最有效和最有效的策略 其目的是：2)调查儿童艾滋病毒治疗启动战略的临床结果和成本效益；3)预测监测艾滋病毒感染儿童一线治疗和改用二线治疗战略的临床和经济结果。通过反映南非和科特迪瓦之间的关键比较，这些分析将代表非洲艾滋病毒流行的许多临床和经济状况。该项目减少艾滋病毒相关发病率和死亡率的目标与任务一致 NICHD：确保所有儿童都有机会充分发挥其健康和富有成效的生活的潜力，不受疾病或残疾的影响。该项目进一步满足了艾滋病研究办公室、PEPFAR《拯救生命路线图》以及千年发展目标6和4的主要目标：优先开展对妇女和弱势儿童的研究，确保儿童普遍获得艾滋病毒治疗，并在全球范围内降低五岁以下儿童死亡率。

DESCRIPTION (provided by applicant): Programs to promptly diagnose and treat pediatric HIV infection play a critical role in reducing childhood mortality in sub-Saharan Africa. Clinical leaders and policymakers need to understand the long-term benefits and costs of these programs, which may differ in settings with different types of HIV epidemics. South Africa is a middle-income country with a very high HIV prevalence (30%: a "generalized" HIV epidemic) and excellent access to health services for HIV-infected women and their infants. C¿te d'Ivoire is a low-income country with a lower HIV prevalence (3%: a "mixed" HIV epidemic) and more limited access to HIV-related health services. These two countries represent two of the key types of HIV epidemic in sub-Saharan Africa. The long-term outcomes of pediatric HIV treatment reflect a continuum of events over decades, and thus cannot be fully investigated using traditional methodologies, such as clinical trials or cohort studies. Computer models can add great value to shorter-term clinical studies by projecting survival and healthcare resource utilization over both short and long time horizons; this can assist clinicians and policymakers in prioritizing among many competing demands for limited resources. In addition, computer models can identify factors that will have the greatest influence on survival and costs, and thus outline critical priorities for future research. Through K01 AI078754 and the IMPAACT network, NICHD, NIAID, and NIMH have supported a preliminary model of pediatric HIV disease, the Cost-effectiveness of Preventing AIDS Complications (CEPAC)-Pediatric model. We have assembled an international research team with expertise in pediatric HIV, simulation modeling, and epidemiology, and we have used the CEPAC-Pediatric model to conduct analyses of strategies to prevent pediatric HIV infection that have informed WHO guidelines. We now propose a major expansion of the CEPAC-Pediatric model and the use of our model to evaluate novel strategies to diagnose and treat pediatric HIV in South Africa and C¿te d'Ivoire. Our three specific aims are: 1) to determine the most effective and efficient strategies for early infant HIV diagnosis; 2) to investigate the clinical outcomes and cost- effectiveness of HIV treatment initiation strategies for children; and 3) to project the clinical and economic outcomes of strategies for monitoring 1st-line therapy and switching to 2nd-line therapy for HIV-infected children. By reflecting key comparisons between South Africa and C¿te d'Ivoire, these analyses will represent many of the clinical and economic conditions that characterize the HIV epidemic in Africa. The project's goals to reduce HIV-related morbidity and mortality align with the mission of NICHD: to ensure that all children have the chance to achieve their full potential for healthy and productive lives, free from disease or disability. The project further meets key goals of the Office of AIDS Research, the PEPFAR "Roadmap for Saving Lives," and Millennium Development Goals 6 and 4: to prioritize research for women and vulnerable children, to ensure universal access to HIV treatment for children, and to reduce under-five mortality worldwide.